Abstract: Lung cancer remains a significant global health concern due to frequent late-stage diagnosis. Although intense research efforts are devoted to developing treatment options, the alterations in lung parenchyma are less explored. In this study, we developed an extracellular matrix (ECM)-based hydrogel by decellularizing lung tissue and combining it with gelatin methacrylate (GelMA) to recapitulate stromal tissue and explore ECM remodeling. About 98% of DNA was removed with the optimized decellularization protocol, while collagen and elastin were preserved at 70% and 62%, respectively. Notably, the sulfated glycosaminoglycan (sGAG) content remained nearly unchanged. Lung-cancer cells were embedded in hydrogel containing dlECM (decellularized lung ECM) and GelMA to form a tumor focus, while lung fibroblast cells were seeded around the focus, and lung epithelial cells were layered on top of the hydrogel, forming the tissue construct of the dynamic tumor-stroma interface-on-chip, which was operated for 14 days. Rheological analysis showed that the tumor model exhibited a higher storage modulus (SM, G') (154.7 Pa) compared to the healthy one (108.29 Pa), indicating a stiffer ECM, which was correlated with increased collagen (400.80 μg/mL vs. 218.56) and elastin (2644.40 vs. 1612.07 μg/mL). This contributed to tumor progression through cancer-driven ECM remodeling. In addition, MMP-2 (31.8 ng/mL) and MMP-9 (7.4 ng/mL) levels, which are associated with tumor progression, were significantly elevated on day 7. Our hybrid hydrogel demonstrated the critical role of ECM in lung-cancer progression by revealing biochemical and mechanical changes in the tumor microenvironment (TME); we anticipate that this will provide critical insights into disease progression.